The development of new pharmaceutical compounds is often impaired by their problematic aqueous solubility, which leads to incomplete dissolution into the gastro-intestinal juices and hence, insufficient bioavailability. Therefore, the improvement of dissolution and solubility of poorly soluble drugs is a major field of interest for formulation scientists. The formulation of solid dispersions, which are prepared by dispersing the poorly soluble active compound into an inert hydrophilic carrier at the solid state, is a possible means of increasing bioavailability.
WO 03/063822A discloses a process for producing a pharmaceutical composition comprising the steps: (a) forming a feed solution comprising a drug, a concentration-enhancing polymer and a solvent; (b) directing said feed solution to a spray-drying apparatus comprising (i) a drying chamber having a volume Vdryer and a height H, (ii) atomizing means for atomizing said feed solution into droplets, (iii) a source of heated drying gas for drying said droplets, said source delivering said drying gas to said drying chamber at a flow rate of G, and (iv) gas-dispersing means for dispersing said drying gas into said drying chamber, said gas-dispersing means causing organized plug flow of said drying gas, wherein Vdryer, is measured in m3, H is at least 1 m, G is measured in m3/sec, and wherein the following mathematical relationship is satisfied [Vdryer/G]≧10 seconds; (c) atomizing said feed solution into droplets in said drying chamber by said atomizing means, said droplets having an average diameter of at least 50 μm and a D10 of at least 10 μm; (d) contacting said droplets with said heated drying gas to form particulates of a solid amorphous dispersion of said drug and said concentration-enhancing polymer; and (e) collecting said particulates, wherein said concentration-enhancing polymer is present in said solution in an amount sufficient that said solid amorphous dispersion provides concentration enhancement of said drug in a use environment relative to a control composition consisting essentially of an equivalent amount of said drug alone.
WO 2005/011636A discloses a process for forming a pharmaceutical composition comprising a solid amorphous dispersion comprising a drug and a polymer, comprising the steps of: (a) providing a drying apparatus having an atomizer connected to a drying chamber, said drying chamber having an inlet and an outlet; (b) forming a spray solution by dissolving said low-solubility drug and said polymer in a solvent, wherein said polymer is selected from the group consisting of hydroxypropyl methyl cellulose acetate succinate, hydroxypropyl methyl cellulose, hydroxypropyl methyl cellulose phthalate, carboxymethyl ethyl cellulose, cellulose acetate phthalate, and cellulose acetate trimellitate; (c) spraying said spray solution through said atomizer into said chamber to form droplets having a volume average size of less than 500 μm; (d) flowing a drying gas through said inlet at a flow rate and a temperature Tin such that said droplets solidify in less than about 20 seconds to form said solid amorphous dispersion of said low-solubility drug in said polymer; (e) wherein said solid amorphous dispersion of said low-solubility drug in said polymer provides either concentration enhancement or faster dissolution of said low-solubility drug in an aqueous use environment relative to a control composition consisting of said low-solubility drug alone; wherein a feed rate of said spray solution is at least 10 kg/hr, and said feed rate of said spray solution and said Tin of said drying gas are controlled so that said drying gas at said outlet has a temperature Tout, and said Tout is less than said boiling point of said solvent.
US 2008/0248117A corresponding to PCT/EP2006/062788 published as WO 2006/0131481A on Dec. 14, 2006 discloses a process for producing solutions in powder or granule form of slightly soluble substances, wherein said slightly soluble substance is in the form of a molecular dispersion in an excipient matrix, comprising atomizing a solution of the active ingredient and matrix excipients by heating an aqueous suspension of said slightly soluble substance in the presence of the matrix excipients to temperatures above the boiling point under atmospheric pressure, dissolving the slightly soluble substance, and converting said solution of slightly soluble substance and matrix excipients by atomizing and drying into a solid form, wherein the temperature of the spray solution before feeding into the atomizing apparatus is in the range of from 90° C. to 350° C.
WO 2007/115381A with the same inventors as the present application discloses a medical dosage form of enhanced solubility and dissolution rate in an aqueous environment of low aqueous solubility drugs, characterised in that it comprises a solid dispersion of at least one drug of low aqueous solubility in graft copolymer of 1) water-soluble chains of the vinyl polymer on 2) a polymer chain of water-soluble waxy of alcohols with general formula C2nH4n+2On+1 or a polymer chain of polyethylene glycols, polyalkylene glycols, polypropylene glycols, polyisobutylene glycols or polymethyl-pentene glycols. WO 2007/115381A further discloses that the form of solid dispersions of drug in the graft copolymer may be obtainable by hot-stage extrusion or spray-drying.
WO 2008/016260A published Feb. 2, 2008 discloses a method of preparing a solid dispersion comprising the steps of: dissolving fenofibrate in an organic solvent, and mixing with 20-200 parts by weight of a water-soluble polymer and 5-50 parts by weight of a surfactant on the basis of 100 parts by weight of fenofibrate to produce a mixed solution, and spray-drying the mixed solution to obtain a solid dispersion comprising an amorphous fenofibrate.
WO 2008/077591A published Jul. 3, 2008 discloses a process for making a solid dispersion, said solid dispersion comprising (4R)-4-[N′-methyl-N′-(3,5-bistrifluoro-methyl-benzoyI)-amino]-4-(3,4-dichlorobenzyl)-but-2-enoic acid N-[(R)-ε-caprolactam-3-yl]-amide or a pharmaceutically acceptable salt or solvate thereof, and a carrier, said process comprising the steps of (a) dissolving or suspending (4R)-4-[N′-methyl-N′-(3,5-bistrifluoromethyl-benzoyl)-amino]-4-(3,4-dichlorobenzyl)-but-2-enoic acid N-[(R)-ε-caprolactam-3-yl]-amide or a pharmaceutically acceptable salt or solvate thereof and the carrier in a solvent to form a solution or suspension; and (b1) spray drying the solution or suspension to give a solid dispersion in dry powder form or (b2) or spray granulating the solution or suspension on at least one inert filler excipient and at least one anti-sticking agent.
U.S. Pat. No. 6,077,543 discloses a method for preparing a dry powder composition, said method comprising: preparing an aqueous solution of a hydrophilic component; preparing an organic solution of a hydrophobic component in an organic solvent; and delivering the aqueous solution containing the hydrophilic component to an atomizer; delivering the organic solution containing the hydrophobic solution to the atomizer separately from the aqueous solution containing the hydrophilic solution; atomizing the two solutions together in the atomizer to produce droplets containing both solutions; spray drying the droplets of the aqueous solution and the organic solution to form dry particles comprising a mixture of the hydrophilic and hydrophobic component, the hydrophobic component preferably comprising a hydrophobic drug.
U.S. Pat. No. 5,985,248 discloses a method for preparing a dry powder composition, said method comprising: at least partially dissolving a hydrophilic component consisting of a hydrophilic excipient or mixture of excipients in an organic solvent or cosolvent system; at least partially dissolving a hydrophobic component consisting of a hydrophobic drug in the same organic solvent or cosolvent system to produce an organic solution, wherein the organic solvent or cosolvent system is selected so that the hydrophilic component has a concentration in the range from 1 mg/ml to 100 mg/ml and the hydrophobic component has a concentration in the range from 0.01 mg/ml to 10 mg/ml; and spray drying the organic solution, to form particles comprising a mixture of the hydrophilic and hydrophobic components, the hydrophobic component preferably comprising a hydrophobic drug.